INERT METAL ION PROTECTING GROUPS IN PEPTIDE SYNTHESIS

合成肽方法具有共同的氨基酸末端保护作用 和侧链来帮助引导多肽的形成。在合成肽的过程中 这些保护基团的性质对成功 综合。这些保护基团中的一些使多肽片段不能溶解 因此限制了合成。 提出了用金属离子保护基团来替代和补充其他有机化合物 组。金属离子的吸引人的特征包括它们的电荷、颜色和易用性。 引入和移除。金属离子保护的正电荷 组可以是一个句柄，它将显著帮助提纯 在合成过程中的任何阶段的合成肽。运动惰性金属 离子可以像有机保护基团一样稳定，但很容易被移除 在非常温和的条件下(通过利用它们的氧化还原特性)。 我们建议使用动力学惰性金属离子，特别是 ((NH3)5Co(III)-)和其他钴(III)衍生物，以帮助在 多种方式：(A)作为C-和N-端的保护基团；(B)作为 各种氨基酸侧链的保护基团；(C)加入 建议将钴(III)添加到聚合物载体上以允许去除 在非常温和的条件下从聚合物载体中得到多肽；最后，(D) 用这些方法探讨了在水溶液中合成多肽的问题 可在非常温和的条件下去除的水溶性金属离子保护基团 条件。 血管紧张素II，一种八个残基的多肽，将用 钴(III)保护基团，以证明这一方法的有效性。

Synthetic peptide methods share in common the protection of amino acid terminals and side chains to help direct peptide formation. During peptide synthesis the properties of these protecting groups become vital to the success of the synthesis. Some of these protecting groups render peptide fragments insoluble and therefore limit the synthesis. Metal ion protecting groups are proposed to replace and complement other organic groups. Attractive features of metal ions include their charge, color, and ease of introduction and removal. The positive charge of the metal ion protecting group can be a handle which will significantly aid in the purification of the synthesized peptide at any stage during the synthesis. Kinetically inert metal ions can be as stable as organic protecting groups, yet can be easily removed under very mild conditions (by making use of their redox properties). We are proposing to use kinetically inert metal ions, especially ((NH3)5Co(III)-) and other cobalt (III) derivatives, to aid peptide synthesis in a variety of ways: (a) as a protecting group for C-and N-terminals; (b) as a protecting group for various amino acid side chains; (c) the incorporation of cobalt(III) onto a polymeric support is suggested to allow the removal of a peptide from the polymeric support under very mild conditions; and finally, (d) the subject of peptide synthesis in aqueous solution is approached using these water soluble metal ion protecting groups which can be removed under very mild conditions. Angiotensin II, an eight residue polypeptide, will be synthesized using cobalt(III) protecting groups to demonstrate the usefulness of this approach.